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Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma

Background: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tiss...

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Autores principales: He, Jingyu, Ouyang, Simin, Zhao, Yilong, Liu, Yuqi, Liu, Yaolong, Zhou, Bing, Man, Qiwen, Liu, Bing, Wu, Tianfu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952890/
https://www.ncbi.nlm.nih.gov/pubmed/36830672
http://dx.doi.org/10.3390/biom13020303
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author He, Jingyu
Ouyang, Simin
Zhao, Yilong
Liu, Yuqi
Liu, Yaolong
Zhou, Bing
Man, Qiwen
Liu, Bing
Wu, Tianfu
author_facet He, Jingyu
Ouyang, Simin
Zhao, Yilong
Liu, Yuqi
Liu, Yaolong
Zhou, Bing
Man, Qiwen
Liu, Bing
Wu, Tianfu
author_sort He, Jingyu
collection PubMed
description Background: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. Methods: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan–Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene–drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. Results: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene–drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). Conclusions: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
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spelling pubmed-99528902023-02-25 Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma He, Jingyu Ouyang, Simin Zhao, Yilong Liu, Yuqi Liu, Yaolong Zhou, Bing Man, Qiwen Liu, Bing Wu, Tianfu Biomolecules Article Background: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. Methods: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan–Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene–drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. Results: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene–drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). Conclusions: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis. MDPI 2023-02-06 /pmc/articles/PMC9952890/ /pubmed/36830672 http://dx.doi.org/10.3390/biom13020303 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
He, Jingyu
Ouyang, Simin
Zhao, Yilong
Liu, Yuqi
Liu, Yaolong
Zhou, Bing
Man, Qiwen
Liu, Bing
Wu, Tianfu
Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title_full Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title_fullStr Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title_short Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma
title_sort prognostic value of cav1 and cav2 in head and neck squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952890/
https://www.ncbi.nlm.nih.gov/pubmed/36830672
http://dx.doi.org/10.3390/biom13020303
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